Hypertrophic Cardiomyopathy (HCM)



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Hypertrophic Cardiomyopathy (HCM) Evaluation and Differential Diagnosis Role of Echocardiography William K. Freeman, MD, FACC, FASE

DISCLOSURES Relevant Financial Relationship(s) None Off Label Usage None

Hypertrophic Cardiomyopathy Echocardiographic Diagnosis Left Ventricular Hypertrophy 15 mm (Asymmetric >> Symmetric) In the absence of another cardiovascular or systemic disease associated with LVH or myocardial wall thickening Gersh, BJ, et al. JACC 2011; 58: e212 ACC/AHA Guidelines

Hypertrophic Cardiomyopathy Echocardiographic Diagnosis Not Mandatory for Diagnosis of HCM Asymmetric Septal Hypertrophy (ASH) Systolic Anterior Motion (SAM) Dynamic LVOT obstruction

Hypertrophic Cardiomyopathy Distribution of LVH (600 Patients) Anterior septum only (25%) Septum & ant lat freewall (17%) Septum & all freewalls (17%) Lateral freewall (1%) Anterior and inferior septum (31%) Anterior septum & ant lat freewall (7%) Apex only (2%) Klues HG, JACC 1995; 26: 1699

Left Ventricular Morphology in HCM Sigmoid Septum Reverse Septum Neutral Septum Apical Variant 181(47%) Gene + (8%) 132(35%) Gene + (79%) 32(8%) Gene + (41%) 37(10%) Gene + (32%) Binder J, et al. Mayo Clin Proc 2006; 81: 459.

Genetic testing for HCM Mayo Clinic Database (389 Patients) Echocardiographic anatomic phenotypes are not specific for individual gene mutations Specific gene mutations not predictive of prognosis or need for myectomy Van Driest SL, et al. Mayo Clin Proc 2005; 80: 739

LVH in HCM: Sigmoid Septum

LVH in HCM: Neutral Septum

LVH in HCM: Reversed Septum

Systolic Anterior Motion (SAM)

HOCM: Systolic Anterior Motion (SAM) Drag effect >>> Venturi effect Anterior displacement of mitral valve and support apparatus; small LV cavity Septal encroachment into LVOT Mitral valve characteristics Anterior displacement of papillary muscles Unusual chordal attachments Elongated anterior leaflet Aberrant muscle bundles

Normal Anatomy of the LV Outflow Tract

Hypertrophic Cardiomyopathy

Systolic Anterior Motion (SAM)

Systolic Anterior Motion (SAM): LV Ejection Obstruction Regurgitation

Systolic Anterior Motion (SAM): LV Ejection

Systolic Anterior Motion (SAM): LV Ejection Obstruction

Systolic Anterior Motion (SAM): LV Ejection Obstruction Regurgitation

Systolic Anterior Motion (SAM): LV Ejection Obstruction Regurgitation

Basal LVOT Obstruction

Basal LVOT Obstruction

Dynamic LVOT Obstruction vs. MR CW Doppler (ΔP 4V 2 ) MR LVOT

HCM Morphology and LVOT Obstruction Mayo Clinic HCM Database (2,856 Patients) Resting Gradient <30 mmhg Provocable Gradient > 30 mmhg (27%) Mid-Cavity Obstruction (2%) Nonobstructive (23%) Resting Gradient >30 mmhg (41%) Apical HCM (7%) Ommen SR, et al. 2006

39 y/o Executive: New DOE during workouts Focal Anteroseptal Basal LVH = 17 mm

39 y/o Executive: New DOE during workouts Rest

39 y/o Executive: New DOE during workouts Rest

39 y/o Executive: New DOE During Workouts Resting LVOT gradient = 12 mmhg

39 y/o Executive: New DOE During Workouts Valsalva Maneuver

39 y/o Executive: New DOE During Workouts Valsalva Maneuver

39 y/o Executive: New DOE During Workouts Valsalva: LVOT gradient = 34 mmhg

39 y/o Executive: New DOE During Workouts Amyl Nitrite

39 y/o Executive: New DOE During Workouts Amyl Nitrite

39 y/o Executive: New DOE During Workouts Amyl Nitrite: LVOT gradient = 77-100 mmhg MR 6.9 m/sec 4.4 m/sec 5.0 m/sec LVOT

Estimating LVOT Gradient Using MR Peak Velocity MR Velocity = 6.9 m/sec Systolic BP = 100 mmhg LV LV Pressure 205 P 4 (6.9) 2 = 190 LVOT gradient 105 LAP 15 LA Aortic Systolic BP = 100 Ao

Mid-Cavitary LVOT Obstruction

Mid-Cavitary LVOT Obstruction

Mid-Cavitary LVOT Obstruction Asymmetric Inferior & Inferoseptal LVH

Mid-Cavitary LVOT Obstruction Asymmetric Inferior & Inferoseptal LVH

Mid-cavitary LVOT Gradient: 56 mmhg

LVOT Obstruction in HCM: More than SAM Alone Abnormal Mitral Support and Muscle Bundles

LVOT Obstruction in HCM: More than SAM Alone Abnormal Mitral Support and Muscle Bundles

LVOT Obstruction in HCM: More than SAM Alone Abnormal Mitral Support and Muscle Bundles

Apical HCM

Apical HCM

Apical HCM

Apical HCM

Apical HCM

Apical HCM with Apical Aneurysm

Apical HCM with Apical Aneurysm

Apical HCM with Apical Aneurysm

Apical HCM with Apical Aneurysm Early and Late Systolic Outflow Obstruction ~ 60 mmhg Systolic Diastolic

Hypertrophic Cardiomyopathy Complicated by Apical Aneurysm Apical abnormalities in apical HCM: Pouch: 15%; Aneurysm: 3% Adverse events associated with aneurysm (not apical pouch) Progressive heart failure/death (18%) SCD or revived cardiac arrest (14%) Appropriate ICD discharge (11%) Nonfatal embolic stroke (7%) Binder J et al JASE 2011;24:775 Maron MS, et al. Circulation 2008;118:1541

Hypertrophic Cardiomyopathy Differential Diagnosis of Thickened LV Walls Acquired Hypertension Aortic stenosis Athlete s heart Cardiovascular Systemic Disease

82 y/o Man: Hypertension x 30 yrs; No Sxs

34 y/o Triathlete: LVH on ECG, No Symptoms LV wall thickness 13 mm

Athlete s Heart versus HCM HCM Athlete s Heart LV wall thickness 15 mm < 15 mm (usually < 13 mm) Morphology Asymmetric Symmetric LVEDD <45mm >55mm Diastolic filling Abnormal Normal LA volume Increased Normal Response to deconditioning None Regression of LVH Strain Imaging* Abnormal Normal Maron BJ. Heart 2005; 91: 1380 * Butz T, et al. Int J Cardiovasc Imaging 2011; 27:101

Hypertrophic Cardiomyopathy Differential Diagnosis of Thickened LV Walls Acquired Hypertension Aortic stenosis Athlete s heart Cardiovascular Systemic Disease Congenital Subaortic stenosis LV noncompaction

71 y/o Woman: Murmur Since Childhood; Previously Treated as HOCM Congenital Fibromuscular Subaortic Stenosis

68 y/o Woman: Abnormal ECG; Asymptomatic Left Ventricular Noncompaction Syndrome

68 y/o Woman: Abnormal ECG; Asymptomatic Left Ventricular Noncompaction Syndrome

Hypertrophic Cardiomyopathy Differential Diagnosis of Thickened LV Walls Acquired Hypertension Aortic stenosis Athlete s heart Cardiovascular Systemic Disease Congenital Subaortic stenosis LV noncompaction Fabry disease Cardiac amyloidosis Hypereosinophilic syndrome

70 y/o Man: Dyspnea on exertion Fabry Disease (Alpha-Galactosidase A Deficiency) Glycosphingolipid Accumulation Pieroni M, et al. JACC 2006; 47: 1663 Hyper-refractile subendocardial border: 94% Sensitive 100% Specific

56 y/o Woman: Biventricular heart failure; SAM Amyloid Infiltrative Cardiomyopathy

Amyloid Infiltrative Cardiomyopathy Low voltage QRS Anteroseptal Pseudoinfarction Pattern

Risk Stratification in HCM Sudden Cardiac Death

Hypertrophic Cardiomyopathy (HCM) Arrhythmogenic Myocardial Substrate Myocyte Disarray Coronary Arteriole Remodeling Ischemia Micro-infarction Fibrosis Maron BJ. Circulation 2010; 121: 445

Sudden Cardiac Death (SCD) in HCM Primary Risk Factors SCD in 1º relative due to HCM Unexplained syncope ( 1 episode) Massive LVH ( 30 mm thickness) Nonsustained VT on ECG monitoring Exercise BP response : or Gersh, BJ, Maron BJ et al. JACC 2011; 58: e212 ACC/AHA Guidelines

HCM with massive (>30 mm) LV hypertrophy Septum: 42 mm; LV mass index 548 gm/m 2

HCM with massive (>30 mm) LV hypertrophy Septum: 42 mm; LV mass index 548 gm/m 2

5 Year mortality Risk Stratification for Sudden Cardiac Death LV Wall Thickness and Clinical Risk Factors 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.00 3 2 1 0 >30 25-29 20-24 15-19 Maximum LV Wall <15 Thickness (mm) Number of Risk Factors Elliot PM, et al. Lancet 2001; 357: 420

Sudden Cardiac Death (SCD) in HCM Secondary Risk Factors Intramyocardial Fibrosis: Delayed gadolinium enhancement on MRI Apical LV aneurysm (Apical variant of HCM) Prior alcohol septal ablation Burning out phase of HCM (1-5% incidence) LVOT obstruction > 30 mmhg at rest ( 10% Positive Predictive Value) Gersh, BJ, Maron BJ et al. JACC 2011; 58: e212 ACC/AHA Guidelines

Intramyocardial Fibrosis in HCM Delayed Gadolinium Enhancement (DGE) on MRI Focal: Low Risk Confluent: Higher risk

Intramyocardial Fibrosis in HCM Delayed Gadolinium Enhancement (DGE) on MRI Predictors of DGE Reversed septal morphology Septal thickness > 20 mm LV Mass > 150 gm/m 2 LVEF < 50% % 60 40 20 0 Nonsustained VT (43 14 Months F/U) 27 8 DGE Present DGE Absent (n = 126) (n = 94) Rubinshtein R, et al. Circ Heart Fail 2010; 3:51

Intramyocardial Fibrosis in HCM: Detection by Echocardiography? Abnormal global and/or regional LV systolic function Apparent normal global and regional LV systolic function Fibrosis likely where LV is dysfunctional Speckle Tracking Strain Imaging

Longitudinal Strain Imaging Risk Stratification in HCM Abnormalities in longitudinal strain correlate directly with degree of myocardial fibrosis by DGE on MRI and also LV wall thickness Popovic ZB, et al. J Am Soc Echocardiogr 2008; 21: 129

Longitudinal Strain Imaging Risk Stratification in HCM The presence of strain values of -10% in > 3/18 LV segments is an independent predictor of nonsustained VT (Sensitivity 81%, Specificity 97%) Di Salvo G, et al. J Am Soc Echocardiogr 2010; 23: 581

31 y/o Electrician: Nonexertional presyncope, syncope, exercise induced hypotension, family history of SCD x 3

31 y/o Electrician: Nonexertional presyncope, syncope, exercise induced hypotension, family history of SCD x 3

31 y/o Electrician: Nonexertional presyncope, syncope, exercise induced hypotension, family history of SCD x 3 Longitudinal Strain

31 y/o Electrician: Nonexertional presyncope, syncope, exercise induced hypotension, family history of SCD x 3 Cardiac MR Imaging: Delayed Gadolinium Enhancement

Sudden Cardiac Death (SCD) in HCM Uncertain Risk Factors Gene mutation (>1,000 mutations; 11 genes) Atrial fibrillation Coronary artery bridging Diastolic dysfunction Modifiable Risk Factors Highly competitive sports Coronary artery disease Gersh, BJ, Maron BJ et al. JACC 2011; 58: e212 ACC/AHA Guidelines

Abnormal Relaxation Mildly Elevated Filling Pressure (Grade Ia/IV) MV Inflow Medial TDI E/e' = 0.6 / 0.03 = 20

Irreversible Restrictive Severely Elevated Filling Pressure (Grade IV/IV) MV Inflow Medial TDI e' = 0.03 E/e ' = 1.2 / 0.03 = 40

Restrictive Diastolic Dysfunction Prognosis in HCM (239 Patients) Cumulative HCM-related death (%) 90 80 70 60 50 40 30 20 10 0 0 4 8 12 16 20 Years Log rank p <0.001 Restrictive LV Filling at Initial Evaluation HR: 3.54; 95% CI 1.91-6.57 Non-Restrictive LV Filling at Initial Evaluation Biagini E, et al. Am J Cardiol 2009; 104: 1727

Indications for ICD in Hypertrophic Cardiomyopathy

Prior cardiac arrest or Sustained VT No Family Hx of SCD in first degree relative or Recent unexplained syncope or LV wall thickness 30 mm No Yes Yes ICD Recommended (Class I) ICD Reasonable (Class IIa) Nonsustained VT or Abnormal Stress BP response No ICD Not Recommended (Class III) Yes Other SCD Risk Factors present? Yes ICD Reasonable (Class IIa) No ICD Role Uncertain (Class IIb) Gersh, BJ, Maron BJ et al. JACC 2011; 58: e212 ACC/AHA Guidelines

Family Screening for HCM by Echo Optional unless: < 12 Yrs Old 12 to 18-21 Yrs Old >18-21 Yrs Old Malignant Family Hx Cardiac symptoms Competitive sports Other signs of LVH Every 12 to 18 Months Every 5 Yrs or as per clinical suspicion Gersh, BJ, Maron BJ et al. JACC 2011; 58: e212 ACC/AHA Guidelines

Evaluation of HCM by Echocardiography Comprehensive echocardiography is indispensable for the diagnosis and hemodynamic assessment of HCM Echocardiography plays an important role in the clinical risk stratification and also the interventional management of the patient with HCM